Jul 3, 1982 - phytohaemagglutinin, concanavalin A, pokeweed mitogen, and cytomegalovirus measured by 14C-thymidine incorporation.13 14. Natural killer ...
BRITISH MEDICAL JOURNAL
VOLUME 285
17
3 juLy 1982
don, for his help with flow calibration. We also thank Professor T J H Clark, Dr P J Rees, and Dr G W McMaster for their support of this project.
References I
Wright BM. A miniature Wright peak-flow meter. Br Med
Jf
1978;ii:
1627-8. 2 Hetzel MR, Clark TJH. Comparison of normal and asthmatic circadian rhythms in peak expiratory flow rate. Thorax 1980;35:732-8.
Webb J, Clark TJH, Chilvers C. Time course of response to prednisolone in chronic airflow obstruction. Thorax 1981;36:18-21. Turner-Warwick M. On observing patterns of airflow obstruction in chronic asthma. BrJ Dis Chest 1977;71 :73-86. 5 Bellamy D, Hutchison DCS. The effects of salbutamol aerosol on lung function in patients with pulmonary emphysema. Br J Dis Chest 1981; 75:190-6. 6 Gardener RM, Hankinson JL, West BJ. Evaluating commercially available spirometers. Am Rev Respir Dis 1980;121 :73-82. 7Perks WH, Sopwith T, Brown D, Green M. Should values obtained with a bellows spirometer be converted to BTPS ? Thorax 1981;36:225.
4
(Accepted 5 May 1982)
Severe acquired immunodeficiency in European homosexual men J GERSTOFT, A MALCHOW-M0LLER, I BYGBJERG, E DICKMEISS, C ENK, P HALBERG, S HAAHR, MARIANNE JACOBSEN, K JENSEN, J MEJER, J 0 NIELSEN, H K THOMSEN, J S0NDERGAARD, I LORENZEN
Abstract Four previously healthy Danish homosexual men developed Kaposi's sarcoma or opportunistic infections with fever of unknown origin and lymphadenopathy. One patient died of a Pneumocystis carinii pneumonia. Three patients had defective cell-mediated immunity with absent leucocyte interferon production and decreased proliferative response to mitogens and antigens. T lymphocyte helper subsets and natural killer cell activity were reduced. Unstimulated mononuclear cells produced leucocyte migration inhibitor factor. Two patients were sexual partners and three had never been to the USA, where cases of severe acquired immunodeficiency have been reported. Thus, the syndrome must also be suspected in European homosexual men who present with fever of unknown origin, opportunistic infections, or Kaposi's sarcoma.
Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark J GERSTOFT, MD, senior registrar in rheumatology, department of medicine A MALCHOW-M0LLER, MD, senior registrar in gastroenterology, department of medicine E DICKMEISS, MD, senior registrar, department of serology P HALBERG, MD, associate professor of rheumatology, department of medicine M JACOBSEN, MD, senior registrar, department of pathology K JENSEN, MD, associate professor, department of microbiology H K THOMSEN, MD, senior registrar, department of pathology J S0NDERGAARD, MD, professor, department of dermatology I LORENZEN, MD, professor of rheumatology, department of medicine
Rigshospitalet, University of Copenhagen, Copenhagen, Denmark I BYGBJERG, MD, senior registrar, department of infectious diseases C ENK, MD, research fellow, laboratory of clinical immunology J 0 NIELSEN, MD, senior registrar, department of infectious diseases Institute of Medical Microbiology, University of Aarhus, Denmark S HAAHR, MD, associate professor Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark J MEJER, MD, senior registrar, department of serology
Introduction During the past eight months an increasing number of cases of Kaposi's sarcoma and opportunistic infections have been reported among previously healthy homosexuals in the United States.'-3 The symptoms include persistent fever, weight loss, general lymphadenopathy, and splenomegaly. About half of the patients developed Kaposi's sarcoma, which is rare in the West, except in patients receiving long-term immunosuppressive treatment.4 Others contracted opportunistic infections, among which Pneumocystis carinii pneumonia was the most common. Immunological studies showed a severe defect in cellular immunity,6-8 which may have been a primary factor leading to secondary opportunistic infections and Kaposi's sarcoma. Cytomegalovirus infections may be of pathogenetic importance, but other factors probably also play a part.9 The syndrome has the characteristics of an epidemic in the USA.3 All previously reported cases were in patients living in the USA, except one who made regular visits.'0 We report four Danish cases with all the characteristics of those in the USA, which indicates that the syndrome has spread to Europe. Results of some immunological studies are also presented.
Patients and methods The four patients were admitted to Hvidovre Hospital between August 1980 and December 1981. The hospital serves a population of 200 000 from the urban part of Copenhagen. IMMUNOLOGICAL STUDIES
Mononuclear cells were obtained from heparinised venous blood. Lymphocyte cell markers were identified (a) by the percentage of cells rosetting with untreated sheep red blood cells (E-rosettes)"; (b) by the percentage of membrane-bound immunoglobulin-positive cells using fluorescein-conjugated polyvalent rabbit anti-human immunoglobulins'2 (Dakopatts, Denmark); and (c) the percentage of T lymphocytes (helper/inducer cells) (Leu 3a) and T lymphocytes (cytotoxic/suppressor cells) (Leu 2a) by indirect immunofluorescence using the hybridoma-derived biotin-conjugated anti-Leu 3a and antiLeu 2a antibodies (Becton-Dickinson, USA) and fluorescein-coupled avidin (Becton-Dickinson, USA).
BRITISH MEDICAL
18 Functional
tests
included
responses
to
phytohaemagglutinin,
pokeweed mitogen, and cytomegalovirus measured by 14 C-thymidine incorporation. 13 14 Natural killer cell activity and activity as effector cells in antibody-dependent cellular cytotoxicity in 51Gr-release assays were measured. The Molt-4 cell line (kindly provided by Dr Mikael Jondal, Karolinska Institute, Stockholm) were used as target cells in the assay for natural killer cell activity'5 and IgG-coated DBA-2 mouse mastocytoma cells as target cells in the assay for antibody-dependent cellular CytotoXiCity.1'6 Lytic units (one unit representing the number of cells giving a cytotoxicity of 25%) concanavalin A,
available.) performed
In
cases
at
an
with those
given
are
TABLE i-Clinical features and
IIL
(Data for
case
1 in table II
small violaceous,
non-raised
were
lesions
were
cutaneous
and
mucous
no
present
on
abnormalities.
lesions confirmed
Kaposi's
the face and
Biopsy of the
sarcoma.
Neisseria
gonorrhoeae and Candida albicans were cultured from the rectum and pharynx respectively. He was treated with ampicillin and mycostatin and transferred to another hospital for cancer chemotherapy. He died five months later of Pneumocystis carinii pneumonia. At necropsy the lesions of Kaposi's sarcoma were found in the skin, palate, hypopharynx,
and
Case 2-A
were not
paratracheal lymph nodes. 50-year-old homosexual man
was
referred in
January
laboratory findings in four Danish homosexual men with acquired immunodeficiency Case 1
Age (years) Sexual contacts Drug abuse Fever, weight loss, anaemia, universal lymphadenopathy* Skin/mucosal lesions suggestive of Kaposi's sarcoma Duration of disease (months) Hepatitis B surface antigen Cytomegalovirus titre Chlamydia trachomatis titre (lymphogranuloma test) Serological examination for syphilis Clinical and pathological findings Present condition
Case 4
Case 3
Case 2
27 Case 3
50
37
31
Nitrites
Nitrites
Nitrites
None
Present Present 5
Present Absent 12
Present Absent 23
Present Absent 12
Negative ND Negative Negative Kaposi's sarcoma, P carinii pneumonia, oral candidosis Died
*Soft, non-tender, non-adherent glands measuring up to 2 x 3
TABLE
in table II.
upper limbs. Chest x-ray films showed
summarised in table I and the results of the
in table
also
identical
man with a two-month history weight loss was seen in May 1981. He had previously been well, apart from having secondary syphilis four years earlier, which had been adequately treated. He took amyl and butyl nitrites regularly and had not visited the USA. He had generalised lymphadenopathy, violaceous lesions on the palate, and oral thrush. Ten
Results The clinical data
were
were
Case 1-A 27-year-old homosexual
were
immunological studies
immunological investigations
earlier stage and gave results which
of fever and
calculated as described by Cerottini and Brunner.'17 Lytic activity was measured by the number of lytic units/ 106 mononuclear cells. Monocyte function tests,18 interferon production studies,' leucocyte migration inhibitory factor tests,'9 and purine enzyme
performed as described. Antibodies to cytomegalovirus and Chiamydia trachomatis determined by complement-fixation tests.
2 and 3
3 juLY 1982
285
Case reports
were
assaysas
VOLUME
JOURNAL
CaselI
Negative 1/128 Negative Negative Kaposi's sarcoma, amoebic dysentery Alive, clinically well
Negative 1/64 1/120. Negative
Negative 1/128 Negative Negative
Alive, not improved
Alive, not improved
Clostridium d(fficile colitis, anal ulcers
Oral candidosis
cm. ND = Not determined.
ii-Immunological results (January 1982) Case 2
'White cell count (cells x 101/l)..10-5 Peripheral lymphocyte count (cells x 109/1)..38 E-rosette formation Percentage *.45 Absolute number (cells x 109/1)..171 Surface immunoglobulin-bearing cells Percentage..13 Absolute number (cells x 1061/1..494 T lymphocytes Leu 2a + (suppressor/cytotoxic) (%.53 Leu 3a + (helper) (On1) .10 Lymphocyte transformation by mitogens and antigens Phytohaemagglutinin (40 sLg/ml)..305 Concanavalin A (25 yjg/ml)..1237 Pokeweed mitogen (1/400 dilution)..58 Cytomegalovirus..Decreased .. Natural killer cells (lytic units/106 cells) (O% of normal controls) ..0-2 (1) K-cell activity (lytic units/10' cells) (% of normal controls) Interferon production in lymphocytes by antigens and mitogens (IU/ 10' cells) Sendai virus
Adenosine deaminase..950 Purine nucleoside phosphorylase..4080
5'nucleotidase..82
Monocyte investigations Number (cells x 10'/l)..05 Total yield..Normal Bactericidal activity..Normal
Chemotaxis..Decreased
Immunoglobulins IgA (g/1)..3.33 (g/1)..28-9 IgG IgM (g/l) Complement components (Clq, C3, C4, C5, and C9) and total haemolytic capacity Immune
complexes..Present
ND = Not determined; LIF = Leucocyte miigration inhibitory factor.
3-0-9-0 1-0-4-8
58 0-348
45 0-810
57-81 0-650-2-25
16 96
17 306
12-26 240-730
57
20-34 33-55
964 871 71 ND 1-8 (12) 0-2 (1)
5051-12 667 2645-6816 453-1517
729-19 683 243-6561 9-2187
Present Present
ND ND ND ND ND
764 2496 26
ND ND ND
337-794 3129-6980 35-346
0.1
0-1 ND ND ND
0-2-0-95
1-54 12-4 0-84 Normal Absent
1-14-4-70 7-1-15-0 0-37-1-31
Decreased 8-1 (54) 21 (60)
